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PillsThe acute episode of intoxication and agitation has subsided and your patient is calm. She has been medically cleared and is ready to be moved to a less acute, less monitored portion of the ED to await further assessment and treatment for her underlying psychiatric conditions. As a well-intentioned emergency medicine practitioner, you wish to give your patient the tools she needs to maintain this calm status by restarting her home atypical antipsychotic medication. What is the best way to go about doing this?

While the atypical antipsychotics have generally been considered safer than the first generation agents due to the decreased risk of extrapyramidal side effects at therapeutic doses, this class is not without adverse effects. All of the medications in this class are capable of causing sedation due to their antihistaminergic effects and some of these agents also have an alpha-blockade effect possibly leading to orthostatic hypotension [1].

Re-Initiation Strategy: Atypical Antipsychotic Medication

When faced with the prospect of re-initiation of atypical antipsychotics, it is necessary to determine how long the patient has been without medication if possible. While there is a lack of literature regarding this topic, select medications make reference to re-initiation in their package inserts [4,8,9].These recommendations range from “an interval off” to “more than one week”, possibly indicating that a few missed doses may not have an impact on the re-initiation dose. However, when it is determined that a patient has been without their atypical antipsychotic for a few days to a week or the period of nonadherence is unknown, caution with re-initiation is justified and some package inserts call for restarting the initial dosing titration.

MedicationPackage insert: Day 1 dosingRe-initiation recommendation
Aripiprazole (Abilify)Schizophrenia: 10-15 mg PO Q 24 hours
Bipolar mania: 15 mg PO Q 24 hours
Bipolar mania (adjunctive therapy): 10-15 mg PO Q 24 hours
No recommendations
Asenapine (Saphris)Schizophrenia: 5 mg PO Q 12 hours
Bipolar mania (monotherapy): 10 mg PO Q 12 hours
Bipolar mania (adjunctive therapy): 5 mg PO Q 12 hours
No recommendations
Iloperidone (Fanapt)Schizophrenia: 1 mg PO Q 12 hoursWhen off > 3 days, the initial dosing titration schedule should be followed
Lurasidone (Latuda)Schizophrenia: 40 mg PO Q 24 hours
Bipolar depression: 20 mg PO Q 24 hours
No recommendations
Olanzapine (Zyprexa)Schizophrenia: 5-10 mg PO Q 24 hours
Bipolar disorder: 10-15 mg PO Q 24 hours
No recommendations
Paliperidone (Invega)Schizophrenia: 6 mg PO Q 24 hours
Schizoaffective disorder: 6 mg PO Q 24 hours
No recommendations
Quetiapine (Seroquel)Schizophrenia: 25 mg PO Q 12 hours
Bipolar mania: 50 mg PO Q 12 hours
Bipolar depression: 50 mg PO Q HS
When off ≥ 1 week, the initial dosing titration schedule should be followed
Risperidone (Risperdal)Schizophrenia: 2 mg PO Q 24 hours
Bipolar mania: 2-3 mg PO Q 24 hours
When off for an interval, the initial titration schedule should be followed
Ziprasidone (Geodon)Schizophrenia: 20 mg PO Q 12 hours
Bipolar I disorder: 40 mg PO Q12 hours
No recommendations

*Dosing above is not adjusted for renal or hepatic dysfunction or concomitantly administered interacting medications

Clozapine

Due to the risk of agranulocytosis for which there is a black box warning, all patients prescribed clozapine must be enrolled in a registry which monitors the patient’s white blood cell count and absolute neutrophil count.  As a result, clozapine dosing must be made in collaboration with the patient’s clozapine registry. In addition, clozapine also carries a black box warning for cardiovascular and respiratory effects and states that for patients who have been without clozapine for 2 or more days, they are to start with 12.5 mg once or twice daily [11].

Other Agents

For other agents, the course of action is less clear. Dosing decisions should ideally be made in conjunction with a psychiatric care provider; however this is not always feasible in the ED setting. For patients on atypical antipsychotics without clear re-initiation instructions in the prescribing information and doses higher than initial dosing (see table), consider a dose reduction. Anecdotally, re-initiating the dose at 50-80% of the maintenance dose seems reasonable in hemodynamically stable patients; however, there are not identified data to support this strategy. Regardless of the strategy implored, vigilance is important when re-initiating atypical antipsychotics. This is especially noteworthy in patients who will be in a less monitored area of the department.

Take Home Points

  • Determine how long the patient has been without their atypical antipsychotic if possible.
  • Use caution when re-initiating home doses of atypical antipsychotic agents and consider dosing reductions in patients who have been without their medications for more than a few doses.
  • Clozapine must be ordered in conjunction with the patient’s clozapine registry and when off for 2 or more days usually requires restarting initial dosing.
  • When the maintenance dose is above the initial dosing and re-initiation instructions are not within the package insert, consider a dose reduction (such as restarting  50-80% of the patient’s stabilized dose, depending on the clinical picture) to avoid adverse events, especially in less monitored patients

Reviewer: Clayton English, PharmD, BCPP

Associate Editor: Bryan Hayes, PharmD, DABAT (@PharmERToxGuy)

 

References

  1. Minns AB, Clark RF. Toxicology and overdose of atypical antipsychotic. J Emerg Med. 2012;43:906-13.
  2. Abilify® [package insert]. Tokyo, Japan. Otsuka Pharmaceutical Co; 8/2013.
  3. Saphris® [package insert]. Whitehouse Station, NJ. Merk & Co; 2009. Rev. 3/2013.
  4. Fanapt® [package insert]. East Hanover, NH. Novartis Pharmaceutical Corporation; 1/2013.
  5. Latuda® [package insert]. Marlborough, MA. Sunovion Pharmaceuticals; 7/2013.
  6. Zyprexa® [package insert]. Indianapolis, IN. Eli Lilly & Company. 1997. Rev. 2013.
  7. Invega® [package insert]. Titusville, NJ. Janssen Pharmaceutical, Inc; 2007. Rev 1/2014.
  8. Seroquel® [package insert]. Wilmington, DE. AstraZenica; 2013.
  9. Risperdal® [package insert].  Titusville, NJ. Janssen Pharmaceutical, Inc; 2007. Rev 11/2013.
  10. Geodon® [package insert]. New York, NY. Pfizer; Rev. 1/2014.
  11. Clozapine [package insert]. Morgantown, WV. Mylan Pharmaceuticals Inc. 5/2013

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Jill Logan, PharmD BCPS

Jill Logan, PharmD BCPS

Clinical Pharmacist
Baltimore Washington Medical Center